title: Increased gelatinase B/matrix metalloproteinase 9 (MMP-9) activity in a murine model of acute coxsackievirus B4-induced pancreatitis.
abstract: Infection of mice with coxsackievirus B4 results within days in a severe acute necrotizing pancreatitis, which resolves completely within weeks. Gelatinase B or matrix metalloproteinase 9 (MMP-9) has previously been shown to be involved in several models of pancreatitis, but its role in virus-induced pancreatitis has never been investigated. We here report that MMP-9 levels are markedly increased in the pancreas of mice that developed acute pancreatitis following infection with coxsackievirus B4. Moreover, using in situ zymography, we demonstrated that MMP-9 is active in vivo. Double immunohistochemical analysis revealed that macrophages and neutrophils were the cellular source of MMP-9. Extensive tissue rearrangements involving collagen turnover were observed, and these were associated with extensive pathology and resolution of the disease. In summary, this report demonstrates that acute coxsackievirus B4-induced pancreatitis involves the action of MMP-9, which is mainly originating from macrophages and neutrophils.
authors.affiliation: Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Armando M
authors.initials: AM
authors.lastname: De Palma
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Aelst
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Van den Steen
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology*; D029822:Enterovirus B, Human / Q000502:physiology*; D008049:Lipase / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000201:enzymology; D010179:Pancreas / Q000276:immunology / Q000473:pathology*; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology*; D012367:RNA, Viral / Q000097:blood; D014766:Viremia
chemical_list: D012367:RNA, Viral; D008049:Lipase; D000681:Amylases; D020780:Matrix Metalloproteinase 9